Acc. Chem. Res. 1985,18, 65-72
65
Chromo- and Fluoroionophores. A New Class of Dye Reagents HANS-GERD LOHRand FRITZVOGTLE* Institut fur Organische Chemie und Biochemie, Universitdt Bonn, 0-3500Bonn 1, West Germany Received March 26, 1984 (Revised Manuscript Received July 6, 1984)
Color reactions are popular criteria for the identification and quantitative determination of substances. For alkaline-earth metal ions, dye reagents and color indicators are available that allow titrimetric determination of the ionic content with chelating agents of the EDTA type.l For alkali metal ions however, only a few color reagents were known before 1977: and these do not allow the photometric ion determination of practical samples. New possibilities were opened by the discovery3 and development of the crown ether chemi ~ t r y . ~The selectivity of non-, mono-, and bicyclic oligoethers to alkali- and alkaline-earth metal ions has forced their use for analytical purposes. Beside their application in separation processes5 and ionselective electrodes: optical detection methods are practicable. In the latter case, two procedures are distinguishable: (a) ion-pair extractions with colored, lipophilic anions: (b) complex formation with dye ligands (chromoionophores8), showing ion-specific color changes.
The Concept of the Molecular Chromophore-Ionophore Combination In the alkali- and alkaline-earth metal salt complexes of crown compounds, the positive cation charge influences the donor heteroatoms (0,N, S)and their electronic surroundings by ion-dipole forces. If one of the heteroatoms is a constituent of a mesomeric system, the electronic disturbance propagates through the whole (n + a) system. Due to different influences on the ground and photoexcited states by “crowned” cations, changes occur in the absorption spectra. In 1967 Pedersen used salt-dependent UV-measurements for the characterization of complexation processes with crown ethers containing aromatic structure units.3 However, the determined development of molecular-combined neutral crown dyes with high “color sensitivity” to complexed cations, began a decade laterSg By suited linkages of monoaza-, benzo-, and other crowns with chromophores, we achieved considerable shifts of absorption bands by the use of salts. For the design of chromoionophores, the following aspects are of particular interest: (1) Which kind of chromophores respond highly sensitive to local ebctronic disturbances by cations? (2) What kind of connections between ionophores and chromophores allow the strongest electronic interactions with complexed Hans-Gerd LGhr was born in Germany in 1952. He studied chemlstry engineering from 1973 to 1978 at the Fachhochschuie Aachen, Abt. Juiich, Germany. In 1977 he began his study at the University of Bonn, Germany, where he received his diploma in 1981 and Doctor’s Degree in 1984. Fritz Vi5gtle is Professor and Director at the Institute of Organic Chemistry and Biochemistry, Bonn, West Germany. He began his studies at the University of Freiburg, Breisgau. and received the Doctor’s Degree in 1985 from the University of Heidelberg. After habilltation he Joined the faculty of the University of Wiirrburg in 1969, moving to his present position 5 years later. His research Interests include synthetic methods, cyciophane, crown, and hostlguest chemistry, and helical molecules.
cations? (3) How far can color effects be realized by steric effects on cation complexation? (4) How do complexed cations act on the fluorescence spectra of fluoroionophores? ( 5 ) How and to what extent can chiral chromoionophores differentiate visually between enantiomers? (6) How can chromoionophores be best utilized for analytical and diagnostic purposes, and which further applications are offered? Simultaneous with our development of neutral chromoionophores, Takagi et al. independently synthesized colored crown ether anions,1° having the same construction principle. Mono- and diprotonic chromophores were set into a crown skeleton in such a way that the complexation of positively charged metal ions was accompanied by the dissociation of protons of the chromophore. The purpose of these “acidic” chromoionophores is primarily the improvement of the phase transfer of cations in extraction experiments. Their color effects in such experiments can be referred primarily to the spectral differences of the protonated and deprotonated species. For example, 1 exhibits on deprotonation a color change from yellow (A, = 390 nm) to violet (518 nm). However, the differences between the absorption spectra of the complexes are fairly poor: The absorption maximum of the potassium complex of 1 in 1,2(1) For example, see: (a) Anderegg, G.; Flaschka, H. A.; Sallmann, R.; Schwarzenbach, G. Helu. Chim. Acta 1954,37, 113. (b) Bermejo-Martinez, F. In ‘Chelates in Analytical Chemistry”; Flaschka, H. A., Barnard, A. J., Eds.; Marcel Dekker: New York, 1976. (c) VBgtle, F.; Ohm, C. Chem. Ber. 1984, 11 7, 948 and references cited therein. (2) (a) Lange, B.; Vejdelek, C. J. ‘Photometrische Analyse”; Verlag Chemie, Weinheim/Bergstr., Germany, 1980. (b) Budesinsky, B.; Menclova, B. Chem. Anal. 1967,56, 30. ( 3 ) (a) Pederaen, C. J. J. Am. Chem. SOC. 1967,89,2495. (b) Pedersen, C. J. Ibid. 1967,89, 7017. (4)For recent reviews on crown compounds, see: (a) “Macrocyclic Polyether Syntheses”; Gokel, G. W., Korzeniowski, S.H., Eds.; Springer Verlag: Berlin, 1982. (b) Viigtle, F.; Weber, E. In “The Chemistry of Functional Groups”; Patai,S.,Ed.;Wiley and Sons: Chichester, 1980; Supple. E., Part 1. (c) ‘Progress in Macrocyclic Chemistry”;Izatt, F. M.; Christensen, J. J., Eds.; Wiley: New York, 1979; Vol. 1. (d) Ibid., 1981, VOl. 2. (5) For example, see: (a) Blasius, E.; Janzen, K. P. Top. Curr. Chem. 1981,98, 163. (b) Mitchell, J. W.; Shanks, D. L. Anal. Chem. 1975,47, 462. (c) Jepson, B. E.; Dewitt, R. J . Inorg. Nucl. Chem. 1976,38,1175. (6) (a) Shanzer, A.; Libman, J.; Frolow, F. Acc. Chem. Res. 1983,16, 60. (b) Morf, W. E.; Ammann, D.; Bissig, R.; Pretach, E.; Simon, W. In ‘Progress in Macrocyclic Chemistry“;Izatt,R. M., Christensen, J. J., Eds.; Wiley: New York, 1979; Vol. 1. (c) Schindler, J. G. J . Clin. Chem. Clin. Biochem. 1979,17,573. (7) (a) Takeda, Y.Top. Curr. Chem. 1984,121,l. (b) Kolthoff, I. M. Can. J. Chem. 1981,59, 1548. (c) Frensdorff, H.K. J . Am. Chem. SOC. 1971,93, 4684. (8) We generally signify such molecules as chromoionophores, which contain a chromophore as well as an ionophore moiety. An intramolecular “electronic coupling” between chromo- and ionophore is not a precondition. (9) Dix, J. P.; VBgtle, F. Angew. Chem. 1978,90,893;Angew. Chem., Int. Ed. Engl. 1978, 17, 857. (IO) (a) Takagi, M.; Nakamura, H.; Ueno, K. Anal. Lett. 1977, IO, 1115. (b) Lamb, J. D. Izatt, R. M.; Christensen, J. J.; Eatough, D. L. in‘Coordination Chemistry of Macrocyclic Compounds”;Melson, A. A., Ed.; Plenum Press: New York, 1979. (c) Bubnis. B. P.; Pacey, G. E. Tetrahedron Lett. 1984,25, 1107.
0001-4842185/0118-0065$01.50/0 0 1985 American Chemical Society
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n
,CHROMOPHORE
1 -
Accounts of Chemical Research A
I o N 0 PH 0
Figure 1. Scheme of the molecular construction of a chromoionophore.
+Ca(SCNl2 (4511 + K I (4551 + N a I (4701 Ligand ( 4 7 7 )
W
I
40 0
500
h [nml-
Figure 4. Absorption spectra of the chromoionophore 6: free ligand and in the presence of salts; solvent, acetonitrile (Amu in
400
500
X [nml-
Figure 2. Absorption spectra of the chromoionophore 3 free ligand and in the presence of salts, solvent, acetonitrile (A, in nanometer).13J4
-. 500 600 X [nmlFigure 5. Absorption spectra of the chromoionophore 9: free ligand and in the presence of salts; solvent, acetonitrile (Amm in nan~meters).’~J~
LOO
500
h Inml-
Figure 3. Absorption spectra of the chromoionophore 5: free ligand and in the presence of salts; solvent, acetonitrile (& in nanometer).13J4
dichloromethane lies at 575 nm and of the sodium complex at 571 nm.l’ Hence, there is hardly a differentiation as a consequence of cation influence on the absorption behavior of the anionic chromophore. Therefore the obtained selectivities have to be referred to the position of the extraction equilibria-similar to the extractions with lipophilic color anion^.^ (11)Takagi, M.; Ueno, K. Top. Curr Chem. 1984,121,39.
Donor-Acceptor-Type12 Chromoionophores with Cation-Induced Hypsochromic Band Shifts A simple but effective combination of dyes and crown ethers exists in the formal replacement of amino substituents of chromophores by azacrowns. In the resulting chromoionophoresthe amine nitrogens possess simultaneously an electron-donor function to complexed cations as well as to the chromophore. The majority of the chromoionophores described until now meet this construction scheme.13-15 The absorption bands of the chromoionophores 2-9 in the visible region are all hypsochromically shifted by (12) For the classification of chromophores applied primarily in this review, see: Griffiths, J. ‘Colour and Constitution of Organic Molecules”; Acedemic Press: London, 1976. (13) Dix, J. P.; Vijgtle, F. Chem. Ber. 1980, 113, 457. (14) Dix, J. P.; VBgtle, F. Chem. Ber. 1981, 114, 638. (15) VBgtle, F. Pure Appl. Chem. 1980,52, 2405.
New Dye Reagents
Vol. 18, 1985
alkali- and alkaline earth metal ions.13-15 Mostly, the r0-l
“OnN 0
LIGAND X
A
n
1 N
O N 0 2
2 3
L
7
7 6
CH
a N % H 3
1
I@
2
color shifts induced by doubly charged ions are significantly larger than those of monovalent cations of comparable size (see Figures 2-5). The influence of the ligand ring size on the selectivity is obvious by the rule shift is effected by the that always the strongest ,A, cation (of same charge) which fits best into the ligand cavity. Thus, we observed the largest band shifts of the ligands 2 and 5 with sodium ions in the alkali metal ion series and of the larger crowns 3 and 6 with potassium salts. The related “uncrowned” chromophores mostly show only negligible or no changes in their absorption spectra on addition of salts. The alterations of the electron spectra of the donor-acceptor dyes 2-9 by complexed cations are accompanied by clear color changes. Thus, barium salts effect a yellow coloring of the red-orange solution of the azodye 3. The orange-red color of the stilbene dye 6 shifts to yellow on complexation of K+ and Ca2+ions; with Ba2+ ions the CH&N solution appears nearly colorless. The characteristic blue of the quinone imine dye 9 (phenol blue analogue) turns to yellowish-orange when Ca2+salts are added, whereas red-violet colorings occur with Li+, K+, and Ba2+. The fact that aromatic n-systems can be influenced by direct interactions with alkali- and alkaline-earth metal ions in suited crown ethers has been surmised for some time by different investigators.16 Misumi and co-workers corroborated this hypothesis by ‘H NMR investigations of cyc10phanes.l~ In the course of our work we found an analogous electronic disturbance of the ‘H NMR and, furthermore, of the UV absorption for the azulene ligands 10-12 with complexed cations.18
p’p qy-J
e
O Y @
10
f-oq
11 : n = l 12 n . 2
The visible absorption band of 10 (A, = 618 nm) is = 610 shifted hypsochromically with salts (Ca2+,,A, nm; Ba2+,A, = 612 nm) under considerable extinction growth. Because in this system the chromophore itself does not contain any heteroatoms, the salt-dependent (16) (a) Frensch, K.; Vogtle, F. Tetrahedron Lett. 1977, 2573. (b) Reinhoudt, D. N.; De Jong, F. In ‘Progress in Macrocyclic Chemistry”; Izatt, R. M., Christensen, J. J., Eds.; 1979; Vol. 1, p 157 ff. (17) Kawashima, N.; Kawashima, T.; Otsubo, T.; Misumi, S. Tetruhedron Lett. 1978, 2025. (18)Uhr, H.-G.;Vogtle, F.; Schuh, W.; Puff, H. Chem. Ber. 1984,117, 2839.
67
effects have to be referred to a direct interaction of complexed cations with the n-system (presumably via the negative polarized five-membered ring). Thermodynamic investigations indicate that the observed cation selectivities of the color effects do not correlate with the stability constants of the complexes in each case. The complex formation constants of the ligands 3 , 5 , 6 , and 8 with several alkali- and alkalineearth metal salts were compared with the corresponding ,A, shifts of the comple~es.’~Whereas the largest band shifts are produced mostly by the cation, which optimally fills out the ligand cavity, the next smaller cation (of the same charge) exhibits a higher complex formation constant. Thus, for the stilbene dye 6 in the alkali metal series, the largest A- shift is observed with K+ (cf. Figure 3; “color selectivity”),whereas Na+ shows the highest stability constant (K+, 7 X 102; Na+, 3 X lo3 L-mol-l; “thermodynamic selectivity”). The latter result can be related easily to the positive polarization of the amine nitrogens in the donor-acceptor dyes, which tends to repulse adjacent cations. The observable changes of the absorption spectra can be described satisfactorily by the electrostatic interactions between the complexed cations and the chromophore dipoles: The solvation of alkali- and alkalineearth metal ions occurs “charge controlled”; i.e., the stabilization of the cations in the polarophilic crown ether cavities is primarily steered by charge dipole interactions.20 Conversely, the electronic states of the chromophores are influenced by these ion-dipole forces, depending on the size and direction of the dipole moment (pg and pe). If pg and pe have different values, the ground and photoexcited states are stabilized and destabilized, respectively, to a different extent.21 In consideration, the more the dipole moment alters during the excitation, the more the absorption band shifts. In donor-acceptor chromophores, the electronic excitation is mostly accompanied by a charge density shift in the direction of acceptor substitutents of the chromophore; i.e., increases of the dipole moments take place.22 Because it can be supposed that the amine nitrogen atoms of the chromoionophores 2-9 are positively polarized, the excited states are more strongly destabilized by cations than the ground states, wherefore hypsochromic shifts result. The color effects of the azulene derivatives 10-12 can also be interpreted qualitatively by dipole considerations: Azulene has a dipole moment of p = 2.65 X C-m in the ground state.% It is suggested by theoretical considerations that the five-membered ring is negatively polarized. During the electronic excitation a reversal of the dipole direction occurs, producing a positive partial charge of the five-membered ring.23 A positive (19) Tummler, B.; Fliess, A,; Wolfes, H.; Maass, G.;Dix, J. P.; Vogtle, F., manuscript in preparation. (20) For example, see: (a) Pedersen, C. J.; Frensdorff, H. K. Angew. Chem. 1972,84,16; Angew. Chem., Znt. Ed. Engl. 1972,11,16. (b) Weber, E.; Vdgtle, F. Chem. Ber. 1976, 109, 1803. (21) This consideration corresponds with the well-investigated models of solvatochromism and electrochromism. Cf. Liptay, W. Angew. Chem. 1969,81, 195; Angew. Chem., Znt. Ed. Engl. 1969, 8, 177. (22) (a) Reichardt, C. “Solvent Effects in Organic Chemistry”;Verlag Chemie: Weinheim/Bergstr., Germany, 1979; pp 189-223. (b) Labhart, H. In ‘Optische Anregung organischer Systeme”; Verlag Chemie: Weinheim/Bergstr., Germany, 1966; pp 160-176. (c) Liptay, W. Zbid., pp 263-339. (23) Baumann, W. Chem. Phys. 1977,20, 17.
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I
500
A [nml-
600
Figure 6. Electron spectra of the ligand 13 in acetonitrile and under addition of salts (Amm in n a n ~ m e t e r s ) . ’ ~ . ~ ~
charge (M+) in close contact to the five-membered ring of the azulene therefore stabilizes the ground state energetically and destabilizes the photoexcited states [pe (SI) = -1.88 X C-m, pe (S,) = -1.16 X C-m]. This consideration corresponds to the observed hypsochromic shifts of the ligand 10 on addition of salts.1°
Donor-Acceptor-Type Chromoionophores with Cation-Induced Bathochromic Band Shifts In accordance with the ion-dipole model described before, we obtained bathochromic band shifts when the ionophore part was placed in the molecule in such a way that complexed cations were coordinated with the electron acceptor of the chromophore. Thus, the quinone imine ligands 13 and 14 show significant bathochromic shifts with enhanced extinctions. Concerning the ,A, shifts, the smaller ions Li+ and Mg2+are favored in comparison with large ions of the same charge (Figure 6). Apparently, a charge density controlled selectivity due to the “cavity flexibility” is present for the compounds 13 and 14.14
-L. ,3
-’
18
The 6-aminoazulene derivatives 15 and 16 like the azacoronand-substituted donor-acceptor dyes 2-9 provide ionophores which are electronically coupled with the chromophore via the amine nitrogens. Nevertheless, we found for the ligands 15 and 16 (in contrast to 2-9) bathochromic shifts of the visible absorption bands on addition of salts (Figure 7).24 The high sensitivity and color selectivity of the chromophore 16 to Ba2+,shown in Figure 7, is expressed visually by a color change from (24) Lohr, H.-G.; Vogtle, F. Chem. Ber., in press.
500
600
A [nml-
Figure 7. Electron spectra of ligand 16 in acetonitrile and under addition of salts (Amw in nanometer^).'^,^^
yellowish-orange to blueish-violet. Relatively small alterations of color from orange up to red are gained with other salts (K+, NH4+,Ca2+). For an elucidation of these red-shifts, ion-dipole considerations can serve again. 6-(Dimethylamino)azulene shows negative solvatochromism;24i.e., it can be supposed that the dipole moment is reduced or reversed in ita direction on the electronic excitation (cf. ref 21). Because the amine nitrogen will surely be polarized positively in the ground state, a shift of charge density from the five-membered ring of the azulene in direction of the N-substituted seven-membered ring is implied during the excitation process. Therefore, the amino group has to be considered itself as a part of the electron acceptor of the c h r ~ m o p h o r e . ~ Accordingly, ~ cations complexed by the ligands 15 and 16 will destabilize the ground state and stabilize (or less destabilize) the excited state, causing bathochromic band shifts. In the chromoionophores 17 and 18,complexed cations can interact with the electron donor as well as the electron-acceptor constituents of the chromophores. Whereas the long-wave absorption band of the aminoanthraquinone ligand 18 at 493 nm, ascribed to an intramolecular charge transfer transition,26 is shifted hypsochromically by salts, the shoulder at 317 nm belonging to a quinoid transition moves bathochromic. Similar findings exist for the aminoanthraquinone ligand 17 under the influence of cation^.^' If the aminoanthraquinone derivative 17 is reduced with alkali metals in tetrahydrofuran, radical ion pairs are formed. Their ENDOR spectraz8show a dependence of the coupling constant from the charge and radius of the metal cations, which is typical for strong ion-pair interaction^.^^ (25) Witzinger, R. Chimia 1961, 15, 89. See also ref 12. (26) Singh, I.; Ogata, R. T.; Moore, R. E.; Chang, C. W. J.; Scheuer, P . J. Tetrahedron 1968, 24, 6053. Cf. ref 12. (27) Dix, J. P. Thesis, Universitiit Bonn, Bonn, Germany, 1980. (28) Lubnitz, M.; Plato, M.; MBbius, K.; Biehl, R. J.Phys. Chem. 1979, 83, 3402. (29) Bock, H.; Hierholzer, B.; Vogtle, F.; Hollmann, G. Angew. Chem. 1984,96, 74; Angew. Chem., Int. Ed. Engl. 1984,23, 57.
New Dye Reagents
Vol. 18, 1985
Cyanine-Type Chromoionophores In the absorption spectra of cyanine ligands like 19 there is no observable change which would indicate the uptake of alkali- or alkaline-earth metal ions?27i30 Tfie reason might be the highly symmetric charge distribution in the dye molecules, admitting no or respectively only small changes of the dipole moments on excitati0n.3~
69
4 rr-DONOR 1
f0
c,,
r-ACCEPTOR
I
Figure 8. Principle of the cation-steered charge transfer absorption.36
Cod Chromoionophores with Charge-Controlled Cation Effects The molecular linkage of the ionophore part at the (&)-polarized end of the chromophore (chromoionophores 20-23) guarantees higher complex formation constants. However, the salt-dependent UV-vis spectra reveal a new problem: The interactions of cations with anionic chromophores are considerably stronger than the ion-dipole forces with the coronand. Thus, a thereupon resulting charge density control, which favors doubly charged ions and Li+, can counteract the cation selectivity especially of larger crowns. Accordingly, the azamerocyanines 20 and 21 exhibit the largest hypsochromic band shifts with Mg2+and Ca2+.32 It seems that the coronand skeletons respective to their size disturb or support the specific interactions of the chromophores with cations.
400
450
h [nml-
Figure 9. The influence of alkali metal salts on the charge transfer absorption of ligand 26 (measured gs difference absorption: ligand mmus 3,5-dinitrobenzenoicacid methyl esterss).
The chromoionophore23 with a bicyclic ligand part, an output of industrial investigation^,^^ offers a remarkable selectivity for K+ ions in a water/dioxane/ morpholine mixture, which is only disturbed by Rb+. The occurring color change from pink to blue or violet allows the qualitative'and quantitative determination of K+ ions in the ppm region in homogeneous solutions as well as in test stripes.34
Misumi and co-workers reported a significant selectivity of the (2,4-dinitrophenyl)azophenol22 in a trichloromethane/ pyridine solution. On addition of lithium salts, the yellowish solution (&= = 400 nm) turns to purple-red (LiC1: ,A, = 563 nm), whereas other alkali metal salts are inactive under these condition^.^^ (30) Struck, R.;Vagtle, F., unpublished results. (31) For reviews on cyanine dyes, see: (a) Feichtmayr, F.; Schlag, J. In 'Optische Anregung organischer Systeme", Verlag Chemie, Weinheim/Bergetr., Germany, 1966; pp 356-374. (b) Cf. ref 12 and 22. (c) Fabian, J.; Hartmann, H. "Light Absorption of Organic Colorants"; Springer Verlag: Berlin, 1980. (32) Hollmann, G.; Vijgtle, F. Chem. Ber. 1984,117,1355. (33) (a) Kaneda, T.; Sugihara, K.; Kamiya, H.; Misumi, S. Tetrahedron Lett. 1981,22, 4407. (b) Nakaahima, K.;Nakatsuji, S.; Akiyama, S.; Kaneda, T.; Misumi, S. Chem. Lett. 1982, 1781.
Chromoionophores with Structure-Controlled Effects Among the chromoionophores 1-23, conformational changes during cation complexation do not play a decisive role for observable color effects. In contrast, the ligands 24-28 show intramolecular electron donor-acceptor interactions, which are essentially steered by steric-complexation effects (Figure 8).35 Long-chained electron donor-acceptor (EDA) podands like 26% exhibit considerable extinction increases and bathochromic shifta (Figure 9) on addition of salts, partially accompqied by visually well-perceptible color deepening (pale yellow yellow). Shorter chained ligands (24, 27) show a decrease of extinction and hypsochromic shifts combined with distinct brightening
-
(34) Merck Patent GmbH (Inv. Klink, R.; Bodart, D.; Lehn, J. M.; Helfert, B.; Bitsch, R.) Eur. Pat. Apl. 83100281.1 (14.01.83). (35) VBgtle, F.; Hollmann, G.; LBhr, H.-G. 8. Int. Farbensymposium, Baden-Baden, Sept 1982. (36) LBhr, H.-G.; VBgtle, F. Chem. Ber., in press.
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21
”
-
Figure 10. Model of the chiral recognition of substrates with C1 symmetry (Newman projection H3N+-CSML with S = small, M = medium, L = large) by receptors with (a) C2,(b) D2,and (c) D3 symmetry. ( 0 ) Groups above the macro ring plane (e.g., CONH,). (0) Groups below the macro ring plane. ‘Oh”28
29
of the solutions with Li+ and Na’. An electronic influence on the “donor and acceptor force” of the EDA systems by complexed cations is of less importance for the change of the absorption intensity than steric effect~.~~ As Staab’s group showed, this principle is analogously applicable for monocyclic ligands of the cyclophane type. Thus, the ligand 28 with a “built-in quinhydrone charge transfer indicator” (A,= 462 nm, E = 324) notifies with NaSCN in CHC13 a nearly trebled extinction ( t = 874) and a red-shift of the visible absorption band of 16 nm.37 The fixation of the a-donor and a-acceptor molecular parts in the ligands 24-28 by the cation-induced conformational arrangement of the polyether chain is reversible and can therefore be considered and used as a “switching mechanism”. The reverse aspect, the allosteric influence of the ligand cavity by structurally variable chromophoric framework units, is the topic of a series of investigations with azodye crown ethers (“photoresponsive The azo link, e.g., in the chromoionophore 29, can be converted from the more stable E configuration to the Z form by photoisomerization, modifying the cavity proportions and therewith the complex formation and extraction constants; i.e., the azodye ligands can mediate the conversion of light energy to chemical funct i ~ n . ~ ~ Chiral Chromoionophores The behavior of crown ethers to form complexes with organic ammonium compounds, amino acids, and organic neutral molecules40has led to the use of chiral crown ethers as model compounds for substrate-receptor studies.41 Their ability to discern between differently configurated guest molecules (chiral recognition) was the base for our efforts to synthesize chromoionophores with asymmetric units. They are constructed with the aim of indicating the chiral recognition visually or by UV-vis spectroscopy and therewith to permit conclusions of the configuration of the guest molecules or their enantiomertc purity. For that purpose, dif(37) Bauer, H.; Briaire, J.; Staab, H. A. Angew. CheA. 1983,95,330; Angew. Chem., Int. Ed. Engl. 1983,22, 334. (38) For a recent review on crown ethers with responsive functions, see: Shinkai, S.; Manabe, 0. Top. Curr. Chem. 1984, 121, 67. (39) (a) Shinkai, S.; Nakaji, T.; Ogawa, T.; Shigematsu, K.; Manabe, 0. J. Am. Chem. SOC. 1981, 103, 111. (b) Cf. Shinkai, S.; Minami, T.; Kusano, Y.; Manabe, 0. Ibid. 1982, 104,1967. (40)For a recent review, see: Vogtle, F.; Miiller, W. M.; Watson, W. H. Top. Curr. Chem. 1984,125, 131. Cf. also El-Basyouni, A.; Briigge, H. J.; von Deuten, K.; Dickel, M.; KnBchel, A.; Koch, K. U.; Kopf, J.; Melzer, D.; Rudolph, G. J. Am. Chem. Soc. 1983,105,6568. (41) For reviews on chiral crown ethers, see: (a) Jolley, S. T.; Bradshaw, J. s.;Izatt, R. M. Heterocycl. Chem. 1982, 19, 3. (b) Weber, E.; Reu. 1979, Vogtle, F. Kontakte 1981,1,24. (c) Stoddart, J. F. Chem. SOC. 8, 85. (d) Cram, D. J.; Cram, J. M. Acc. Chem. Res. 1978, 11, 8.
ferently intensive interactions (ion-dipole, dipole-dipole, hydrogen bridges) have to work between the chromophore and the binding site of the enantiomers in their diastereomeric complexes. The chromoionophore 30 is the first chiral dye crown ether synthesi~ed.~~ Due to the azamerocyanine units, which show strong solvatochromism,the optically active ligand is a potential receptor for the differentiation between the enantiomers of optically active substrates (e.g., amines, alcohols, carbohydrates, etc.). However,
30
the discrimination of an enantiomer with 30 could not be ascertained in the UV-vis spectra until Presumably, this has to be referred primarily to a lack of steric interactions between the guest molecules and the periphery of the macro ring. Molecular model considerations as illustrated by the stylized receptorsubstrate models in Figure 10 suggest that especially the D3 symmetry of the ligand 30 is responsible for the insufficient chiral recognition. In the stylized ligands of the symmetry groups Cz and Dz, the different distances of the guest substituents M and S to the lateral groups of the macro ring are immediately obvious. An analogous host-guest interaction with the D3 symmetric ligand does not lead to a sterically conditioned differentiation of the R and S substrate: In the arrangement shown in Figure lOc, the substituents M and S can be exchanged without alteration of the distances to equal groups of the D3 host.43 Only by a declination of the substrate angles from the ideal tetrahedral angle or by a sloping positioned guest molecule, i.e., the nonparallelism of the C-N bond and the C3 axis of the macro ring, distance and energy differences appear in the stereoisomeric complexes. (42) A distinction between the enantiomers of organic ammonium compounds in homogeneous solution is not possible, because a protonation of the dye occurs with RNH3+. Hollmann, G. Thesis, Universitat Bonn, Bonn, Germany, 1983. (43) The two model stereoisomers (Figure 1Oc) remarkably neither indicate different distances between equally built structure units nor are they mirror images of one another: Le., the two represented model associates are isometric diastereomers. Analogous considerations can be made for stereoisomers, which are built by the combination of structures of the symmetry group CBnor D3n(n = 1, 2, 3, ...) with C, symmetric structures.
Vol. 18, 1985
New Dye Reagents
The view is analogously valid for any conformation of the macro ring with D3 symmetry; on each side of the ligand three equal "niches" are steadily provided at the periphery. It seems therefore that mglecular receptors with Czand D, symmetry offer better (pre)conditions for a chiral recognition than ligands with D3 symmetry. This may also be the reason why a successful differentiation of enantiomers by D3 configured crown ethers has not been reported until now.44
Fluoroionophores Because of its high sensitivity and the high selectivity, fluorimetry is. of increasing importance for chemical trace analyses. Due to the formation of metal-chelate compounds, inorganic analyses can be carried out by fluorimetric measurements. For alkaline-earth metal salts, numerous fluorophores with structural elements of the EDTA type are available.45 Alkali metal ions can be determined in extraction processes by ionophores and fluorescent counterions (e.g., eosine).& The phenolic chromoionophores with umbelliferone units show Li+ (31) and K+ (32) affinity in extraction experiment~.~~
31:~=1 32: n= 2
35
,OX"
X
3 8 , 3 9o0 X Xx
Sousa and Larson designed the naphthalene crown8 33-35 as model systems for the study of the geometric
requirements of perturber-chromophore interactions.48 (44) For chiral crowns with D3 symmetry, see ref 41 and (a) Kyba, E. P.; Gokel, G. W.; de Jong, F.; Koga, K.; Sousa, L. R.; Siegel, M. G.; Kaplan, L.; Dotaevi, Y.; Sogah, G. D. Y.;Cram, D. J. J . Org. Chem. 1977, 42, 4173. (b) Curtis, W. D.; Laidler, D. A.; Stoddart, J. F.;Jones, G. H. J. Chem. Soc., Perkin Trans.1 1977,1756. (c) Lehn, J. M.; Vierling, P.; Hayward, R. C. J. Chem. SOC.,Chem. Commun.1979,296. (45) For example, see: (a) Hoelzl Wallach, D. F.; Steck, T. L. Anal. Chem. 1963,35,1035 and references cited therein. (b) Rink, T. J. Pure Appl. Chem. 1983,55,1977. (c) Tsien, R. Y . Biochemistry 1980,19,2396. (46) Sam-Medel, A.; Gomis, D. B. Talanta 1981,28, 430. (47) Nishida, H.; Katayama, Y.; Kabuki, H.; Nakamura, H.; Takagi, M.; Ueno, K. Chem. Lett. 1982,1853.
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An important feature of these molecules is the predetermined orientation of the chromophore and a complexed perturber. The influence of alkali metal ions on the naphthalene derivatives is reflected by the emission properties. Whereas a decrease of the fluorescence quantum yields occurs for the ligands 33 and 35 with alkali metal salts in alcohol glass at 77 K (&, free > NaCl > KC1 > RbCl > CsCl), a distinct increase is observed for 34 (&, RbCl > KC1 > CsCl > NaCl > free). The phosphorescence quantum yields are influenced in the reverse sense, i.e., increase for 33 and 35, decrease for 34. The heavy atom perturbation by Cs+ causes increased rate constants for all three crowns in processes involving singlet-triplet interchange^.^^ Noncyclic fluoroionophores (36 and 37) with diphenylmaleinimide units have been examined by Simon et al. in view of the ionselectivity and transport behavior in membranes and were compared with similar ionophores without chromophore subunits.49 The ligand 36 was proved to be a carrier for Li+ in PVC membrane electrodes, whereas in the one-phase system (ethanol) a high selectivity for Ca2+is revealed by fluorescence quench titrations. Distinctions between the enantiomers of the dipeptides glycine-phenylalanine (Gly-Phe) and glycinetryptophan (Gly-Trp) are assigned by the emission spectra of the chiral coronands 38-40 and the therein complexed guests." From quenching data, Tundo and Fendler obtained the stability constants of the diastereomeric complexes and calculated a "chiral efficiency" of ca. 4-7 % . The anthracenoyl crowns 41-43 from our laboratory have been used as fluorescent probes for the solid-phase transition of phosphatidylcholine^.^^ The least lipophilic compound 41 is excluded from the hydrocarbon phase, whereas the most lipophilic compound 42 is located at the bilayer surface. The anthracenophane cryptand 43 preferentially partitions into solid-phase lecithins with the highest affinity for the phases L, and L,. Fluorescence quenching titrations (with Cu2+, SCN-, N,N-dimethylaniline) suggest that the average position of 43 discontinuously shifts from the glycerol backbone to the choline headgroup during the gel to liquid crj&alline transition. Due to its large change of fluorescence intensity, the fluorophore 43 is a sensitive probe for the detection of pretransition of symmetrically substituted and of the subtransition of asymmetrically substituted phosphatidylcholine^.^^
Conclusions and Future Aspects Although crown ether and dye chemistry are well investigated, the development of chromoionophores was at the beginning connected with problems and unexpected results. Only the synthesis of representative charged and neutral chromoionophores and their thorough spectroscopic investigations gave an insight into cation-chromophore interactions. The ion-dipole model can now serve for the design of new effective dye crown ethers: Accordingly, high dipole-moment changes (48) (a) Sousa, L. R.; Larson, J. M. J. Am. Chem. SOC.1977,99,307. (b) Larson, J. M.; Sousa, L. R. Zbid. 1978, 100, 1943. (49) Villiger, A.; Morf, W. E.; Simon, W. Helu. Chtm. Acta 1983,66, 1078. (50) Tundo, P.; Fendler, J. H. J. Am. Chem. SOC.1979, 101, 1760. (51) Herrmann, U.; TCunmler, B.; Maaas, G.; Koo Tze Mew, P.; VGgtle, F. Biochemistry 1984,23,4059. Tiimmler, B.; Herrmann, U.; Maass, G.; Eibl, H. Biochemistry 1984, 23, 4068.
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Lohr and Vogtle
during the electronic excitation of the chromophore seem to be a necessary precondition for a sensitive cation indication, as well as the construction of bicyclic ionophore parts for the enhancement of the cation selectivity. The linkage of the ionophore at the (&)-POlarked chromophore side-without doubt advantageous for the complex formation constants-might be suited primarily for cations with high charge density. Cation-induced changes of the absorption spectra allow the experimental verification of the dipole direction in chromophores, contributing to the theory and classification of dyes. The principle of the cationsteered charge-transfer absorption ("molecular dye switches") can serve as a visual and photoresponsive
Accounts of Chemical Research
indication for the study of allosteric effects. The determined influence of the fluorescence, the cation-steered chemilumine~cence,~~ as well as the optical enantiomer discrimination with chiral receptor dyes should be realized in the near future. W e thank Prof. V. Prelog, Prof. W. Baumann, Prof. S. Hunig, Prof. H. Balli, Dr. P.Neumann, U.Maurer, and Dr. E. Weber for helpful discussions. I n addition we are most grateful for the basic experimental contributions from Dr. J. P. Dix and Dr. G . Hollmann as cited in some of the references. Our research in this field has been supported partially by the Deutsche Forschungsgemeinschaft and the Fonds der Chemischen Industrie. (52) DuchBne, K.-H.; VBgtle, F., unpublished.
